Aging-related IgG accumulation promotes skin inflammation.

Abstract

Aging skin is characterized by wrinkles, loss of elasticity, and impaired barrier function, largely driven by alterations in dermal fibroblasts and extracellular matrix remodeling. Chronic, age-related inflammation, called inflammaging, is a central activity underlying these changes. Immunoglobulin G (IgG) has recently been shown to accumulate in multiple organs with aging, where it activates macrophages to promote tissue inflammation. However, whether IgG contributes to skin aging remains unknown. Here, using mouse and human tissues we show that IgG accumulates in the dermis with age and promotes dermal inflammation and atrophy. Moreover, experimental IgG administration to young mice induced chemokine expression, facilitating infiltration of skin tissue by macrophages and T cells. These findings support a model whereby IgG activates macrophages to produce chemokines and interleukin-12, enhancing interferon-γ production by T cells and suppressing collagen synthesis in fibroblasts. These findings strongly suggest that IgG drives cutaneous skin inflammation and skin aging via crosstalk between immune cells and fibroblasts, and that targeting IgG accumulation or downstream signaling may delay skin aging and extend tissue healthspan.